People With Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Exhibit Similarly Impaired Vascular Function, 2023, McLaughlin+

E

EndME

Senior Member (Voting Rights)
People With Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Exhibit Similarly Impaired Vascular Function

Background
This study aimed to compare flow-mediated dilation values between individuals with Long COVID, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and healthy age-matched controls to assess the potential implications for clinical management and long-term health outcomes.

Methods
A case-case-control approach was employed, and flow-mediated dilation measurements were obtained from 51 participants (17 Long COVID patients, 17 ME/CFS patients, and 17 healthy age-matched controls). Flow-mediated dilation values were analysed using one-way ANOVA for between-group comparisons.

Results
Results revealed significantly impaired endothelial function in both Long COVID and ME/CFS groups compared to healthy age-matched controls as determined by maximum % brachial artery diameter post-occlusion compared to pre-occlusion resting diameter (6.99 ± 4.33% and 6.60 ± 3.48% vs. 11.30 ± 4.44%, respectively, both p < 0.05). Notably, there was no difference in flow-mediated dilation between Long COVID and ME/CFS groups (p = 0.949), despite significantly longer illness duration in the ME/CFS group (ME/CFS: 16 ± 11.15 years vs. Long COVID: 1.36 ± 0.51 years, p < 0.0001).

Conclusion
The study demonstrates that both Long COVID and ME/CFS patients exhibit similarly impaired endothelial function, indicating potential vascular involvement in the pathogenesis of these post-viral illnesses. The significant reduction in flow-mediated dilation values suggests an increased cardiovascular risk in these populations, warranting careful monitoring and the development of targeted interventions to improve endothelial function and mitigate long-term health implications.

https://www.amjmed.com/article/S0002-9343(23)00609-5/fulltext
 
Uses flow-mediated dilation, which is very similar to EndoPat used by other groups.

A significant problem (in drawing a comparison to HC) here are the large differences in weight/BMI between the ill and healthy patients, with the BMI for LC being at 34.19, for ME/CFS at 31.49, and for HC at 24.23. This alone can be responsible for explaining the differences observed (as well as differences in activity levels affecting vascular function) https://pubmed.ncbi.nlm.nih.gov/14769683/.

However, this is not an issue for the comparison ME/CFS vs LC where, as expected, significant overlaps can be seen. Unfortunately, a comparison to HC doesn't really seem possible (or maybe it does https://www.sciencedirect.com/science/article/abs/pii/S0167527300003818?).

It is worth noting that the large spread of the data shows that some individuals in Long COVID and ME/CFS groups had very severely impaired endothelial function, whilst others had comparable flow-mediated dilation to that of the controls. This suggests possibly different disease trajectories and symptomology amongst individuals with post-viral illnesses which is yet to be explored.
Click to expand...

However, the current study opposes this contention as Long COVID and ME/CFS groups exhibited similar flow-mediated dilation values despite significantly different illness duration (ME/CFS: 16±11.15 years vs Long COVID: 1.36±0.51 years, p <0.0001). Therefore, the impairment in flow-mediated dilation in the current study is unlikely due to deconditioning. It is more likely that endothelial damage is experienced in the early post-viral phase, without further reduction in flow-mediated dilation after this initial diminution.
Click to expand...
 
Last edited:
This seems like a good contribution, replicating Fluge and Mella's Endothelial dysfunction in ME/CFS patients (2023). The key point as quoted above by @EndME is identical findings in ME and LC despite a much longer disease duration in the ME group. So a good argument against deconditioning which might be expected to worsen over time.

I couldn't see a good description of the inclusion criteria beyond "long Covid" and "ME/CFS", but the authors seemed to understand PEM etc well. I appreciated the reference to NICE 21 and comments about lack of inclusion of more severe patients.

It is important to note that our experimental methods constrained participation to individuals who could travel to our laboratory, navigate stairs or lifts, and undergo the testing process. This approach was not entirely inclusive for people with Long COVID and ME/CFS, considering that according to NICE, approximately 25% of individuals with ME/CFS are bedbound or housebound46 , making it impossible for them to visit a laboratory. As a result, the extent of vascular function deficits observed in this study likely underestimates the true effect due to the inherent recruitment bias.
Click to expand...
 
I can’t manage to read this study, could someone tell me how would this be monitored? Are there any existing interventions at all, if so are they rare and expensive or more widely available?

warranting careful monitoring and the development of targeted interventions to improve endothelial function and mitigate long-term health implications.

 
Ash said:
I can’t manage to read this study, could someone tell me how would this be monitored? Are there any existing interventions at all, if so are they rare and expensive or more widely available?

warranting careful monitoring and the development of targeted interventions to improve endothelial function and mitigate long-term health implications.
Click to expand...
This would be an area where lifestyle interventions can easily be recommended. Stop smoking, eat healthy, exercise.. avoid getting infected by a virus that damages the endothelium ;) Though of course how much help there is in changing smoking/eating/exercise habits if the damage is from other causes will be debatable.
 
Midnattsol said:
This would be an area where lifestyle interventions can easily be recommended. Stop smoking, eat healthy, exercise.. avoid getting infected by a virus that damages the endothelium ;) Though of course how much help there is in changing smoking/eating/exercise habits if the damage is from other causes will be debatable.
Click to expand...

If you already have LC damage done and or you can’t avoid getting infected because you're a disabled person who requires services and you’re neither wealthy nor healthy enough to isolate in a lovely cabin in the woods?
 
I was part of this trial. It was a one part of a bigger trial. They are planning to do a large scale trial and are seeking to secure funding.

It's almost conical that when I took my results to the GP. The doppler test result put me in the bottom 5 percentile of the population, he took one look at it and said 'I can't do anything with this, go back to them and maybe they can treat you'.
 
It looks like a nice study, well-explained, with the major problem being the one that @EndME mentioned. The authors too recognise it. Interestingly, they seem to have plotted flow-mediated dilation and BMI and didn't find a result, so possibly there is something going on here beyond deconditioning or obesity causing the lower FMD.

The current study found no relationship between flow-mediated dilation and age (r = -0.179, p = 0.21), BMI (r = -0.097, p = 0.50), systolic BP (r = -0.045, p = 0.75), diastolic BP (r = -0.191, p = 0.18) or heart rate (r = -0.072, p = 0.62). In contrast, a large study investigating flow-mediated dilation reference intervals (n = 5362) found that age was strongly associated with flow-mediated dilation
44
. Perhaps larger participant numbers were required to confirm this effect in the current study. Furthermore, previous studies have found that obesity has an association with flow-mediated dilation
45
. In the current study, BMI was high in both ME/CFS and long COVID groups (34.19 ± 6.14 kg·m2 and 31.49 ± 9.21 kg·m2, respectively) compared to control (24.23 ± 3.62 kg·m2). This may explain the lack of interactions between BMI and flow-mediated dilation in this study and highlights the requirement for further investigation in BMI-matched individuals. Similarly, previous studies have found flow-mediated dilation to relate to systolic and diastolic BP in healthy individuals
44
which is in contrast to the findings in this study. There is no clear explanation for this divergence, warranting further investigation and potential explanations for these differences.
Click to expand...

I'm pretty sure I underwent this investigation when I participated in a 2xCPET study, although I don't think the results of the measurements were published. Is arterial stiffness the same as low flow mediated dilation? My result was not great.

I do think blood flow control is a significant part of the illness. I hope this team get the funding they need for a bigger study with better matched controls.

@kilfinnan, well done to you for participating in the trial. Thank you for your effort. Maybe you could mention to the investigators that it would be great to see a scatter chart of the actual FMD values in the next study?
 
They are looking for potential participants. It would involve 2 visits to a University in the West of Scotland. A week between visits.

The doppler was one day, one test. Included with other tests. Gait sitting standing etc.

I don't know what the significance is of a double visit.

I will post a contact email here when I get one. I should hear from Dr McLaughlan this week. She emailed me last week asking what the ME community would think about further trial. They are very keen to secure Scottish Government funding for this.

I will pass on any comment or opinion regarding the trial.
 
kilfinnan said:
She emailed me last week asking what the ME community would think about further trial. They are very keen to secure Scottish Government funding for this.
Click to expand...

Obviously they may be able to get some ideas from the way DecodeME was set up (some of the approaches could potentially help even with a much smaller trial), but folk here might be able help by offering feedback – their research question, the way they hope to recruit, the screening tools, the reporting, etc? People would also be able to help walk them through how to make the visits to their centre as accessible as possible.

If the team has the resources to do any of that, even informal patient participation ought to help their case for funding.
 
The Science for ME committee has written a letter of support for an ME/CFS research initiative. If a researcher wanted a letter of support from the forum, I expect the committee would consider a request. If it became a regular thing, we could perhaps develop some formal criteria.

As Kitty says, engagement on the forum might be useful and would certainly indicate a commitment to patient participation.
 
Recruited via social media, the study included 51 participants in total – 17 with ME/CFS, 17 with long COVID, and 17 healthy controls. The paper does not mention whether ME/CFS diagnoses were confirmed or, if so, which diagnostic/research criteria were used. Whilst the healthy controls were matched with the disease cohorts in terms of age, there were some substantial differences in body mass index (BMI), blood pressure, and heart rate between the groups.

The authors mention that to “reduce participant burden, participants were not advised to fast before the test”. Yet, they acknowledge that dietary intake immediately prior to flow-mediated dilation assessment can have a potentially confounding effect on the results.

As mentioned in the paper, it might be hypothesised that individuals with ME/CFS would have poorer vascular function than people with long COVID, due to a longer duration of post-viral illness and ‘multi-system deconditioning’ (which is known to reduce flow-mediated dilation). Yet, interestingly, there was no difference in flow-mediated dilation between participants with ME/CFS and those with long COVID. The authors state this could suggest that endothelial damage is experienced in the early post-viral phase, without a further reduction in flow-mediated dilation after this initial reduction, and that impairment in flow-mediated dilation is unlikely to be due to deconditioning.
 
Sorry, it's a bit more complicated than that. And I didn't use proper terminology.

The effect of acute inorganic diatery supplementation on flow-mediated dilation in people with long-COVID and people with ME/CFS: A feasibility and pilot-study.

98% Concentrated Beetroot Juice 2% Lemon Juice.

2 x 70ml beetroot juice on one visit v's 2 x 70ml nitrate depleted beetroot juice. 2 visits.
 
kilfinnan said:
Sorry, it's a bit more complicated than that. And I didn't use proper terminology.

The effect of acute inorganic diatery supplementation on flow-mediated dilation in people with long-COVID and people with ME/CFS: A feasibility and pilot-study.

98% Concentrated Beetroot Juice 2% Lemon Juice.

2 x 70ml beetroot juice on one visit v's 2 x 70ml nitrate depleted beetroot juice. 2 visits.
Click to expand...

Citrulene is a dietary supplement that has also been shown to improve vessel dilation. There are also prescription medications such as erectile dysfunction drugs that help vascular dilation.

My N=1 experiment with citrulene and beet root extract is that they may have improved vessel dilation but it increased orthostatic hypotension. Folks may want to try them though. They could potentially assist with energy production with more blood reaching working cells.
 
  • Like
Reactions: Ash
RobH said:
Citrulene is a dietary supplement that has also been shown to improve vessel dilation. There are also prescription medications such as erectile dysfunction drugs that help vascular dilation.

My N=1 experiment with citrulene and beet root extract is that they may have improved vessel dilation but it increased orthostatic hypotension. Folks may want to try them though. They could potentially assist with energy production with more blood reaching working cells.
Click to expand...

Thanks for that, I'll look into Citrulene. Ivabradine changed my existence. Really good, made a big difference.
 
You must log in or register to reply here.
Back
Top Bottom